title: N-linked glycan in tick-borne encephalitis virus envelope protein affects viral secretion in mammalian cells, but not in tick cells.
abstract: Tick-borne encephalitis virus (TBEV) is a zoonotic disease agent that causes severe encephalitis in humans. The envelope protein E of TBEV has one N-linked glycosylation consensus sequence, but little is known about the biological function of the N-linked glycan. In this study, the function of protein E glycosylation was investigated using recombinant TBEV with or without the protein E N-linked glycan. Virion infectivity was not affected after removing the N-linked glycans using N-glycosidase F. In mammalian cells, loss of glycosylation affected the conformation of protein E during secretion, reducing the infectivity of secreted virions. Mice subcutaneously infected with TBEV lacking protein E glycosylation showed no signs of disease, and viral multiplication in peripheral organs was reduced relative to that with the parental virus. In contrast, loss of glycosylation did not affect the secretory process of infectious virions in tick cells. Furthermore, inhibition of transport to the Golgi apparatus affected TBEV secretion in mammalian cells, but not in tick cells, indicating that TBEV was secreted through an unidentified pathway after synthesis in endoplasmic reticulum in tick cells. These results increase our understanding of the molecular mechanisms of TBEV maturation.
authors.affiliation: Laboratory of Public Health, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yoshii
authors.affiliation: Laboratory of Public Health, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan.
authors.forename: Natsumi
authors.initials: N
authors.lastname: Yanagihara
authors.affiliation: Laboratory of Public Health, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Ishizuka
authors.affiliation: Laboratory of Public Health, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan.
authors.forename: Mizuki
authors.initials: M
authors.lastname: Sakai
authors.affiliation: Laboratory of Public Health, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kariwa
mesh_terms: D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D004669:Encephalitis Viruses, Tick-Borne / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D005260:Female; D015967:Gene Expression Regulation, Viral; D006031:Glycosylation; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D011134:Polysaccharides / Q000737:chemistry*; D013987:Ticks / Q000166:cytology*; D013997:Time Factors; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
chemical_list: D011134:Polysaccharides; D014759:Viral Envelope Proteins